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J Modolell

Publications and source records attributed to J Modolell.

At least 37 records · Page 2Linked to original sources
PubMed1995

Cis-regulation of achaete and scute: shared enhancer-like elements drive their coexpression in proneural clusters of the imaginal discs.

The pattern of bristles and other sensory organs on the adult cuticle of Drosophila is prefigured in the imaginal discs by the pattern of expression of the proneural achaete (ac) and scute (sc) genes, two members of the ac-sc complex (AS-C). These genes are simultaneously expressed by groups of cells (the proneural clusters) located at constant positions in discs. Their products (transcription factors of the basic-helix-loop-helix family) allow cells to become sensory organ mother cells (SMCs), a fate normally realized by only one or a few cells per cluster. Here we show that the highly complex pattern of proneural clusters is constructed piecemeal, by the action on ac and sc of site-specific, enhancer-like elements distributed along most of the AS-C (approximately 90 kb). Fragments of AS-C DNA containing these enhancers drive reporter lacZ genes in only one or a few proneural clusters. This expression is independent of the ac and sc endogenous genes, indicating that the enhancers respond to local combinations of factors (prepattern). We show further that the cross-activation between ac and sc, discovered by means of transgenes containing either ac or sc promoter fragments linked to lacZ and thought to explain the almost identical patterns of ac and sc expression, does not occur detectably between the endogenous ac and sc genes in most proneural clusters. Our data indicate that coexpression is accomplished by activation of both ac and sc by the same set of position-specific enhancers.

Animals↗
PubMed1994

The helix-loop-helix extramacrochaetae protein is required for proper specification of many cell types in the Drosophila embryo.

The Drosophila Extramacrochaetae protein antagonizes the proneural function of the Achaete and Scute proteins in the generation of the adult fly sensory organs. Extra-macrochaetae sequesters these basic-region-helix-loop-helix transcription factors as heterodimers inefficient for binding to DNA. We show that, during embryonic development, the extramacrochaetae gene is expressed in complex patterns that comprise derivatives of the three embryonic layers. Expression of extramacrochaetae often precedes and accompanies morphogenetic movements. It also occurs at regions of specialized cell-cell contact and/or cell recognition, like the epidermal part of the muscle attachment sites and the differentiating CNS. The insufficiency of extramacrochaetae affects most tissues where it is expressed. The defects suggest faulty specification of different cell types and result in impairment of processes as diverse as cell proliferation and commitment, cell adhesion and cell recognition. If Extramacrochaetae participates in cell specification by dimerizing with basic-region-helix-loop-helix proteins, the variety of defects and tissues affected by the insufficiency of extramacrochaetae suggests that helix-loop-helix proteins are involved in many embryonic developmental processes.

Animals↗
PubMed1993

Neural fate specification in Drosophila.

The specification of cell fates, particularly in the nervous system where cell diversity is highest, is a basic problem in developmental biology. Mutational and molecular analyses in Drosophila are uncovering families of genes, many of them transcription factors, that regulate the progressive acquisition of neural traits. These comprise the initial selection of neural precursors from the ectoderm, the implementation of a basic neural fate common to all precursors and the concomitant endowment of each precursor and its progeny with specific fates.

Animals↗
PubMed1993

Regulation of the proneural gene achaete by helix-loop-helix proteins.

The Achaete (Ac) protein, a transcriptional regulator of the basic-helix-loop-helix (bHLH) type, confers upon ectodermal cells the ability to become neural precursors. Its temporally and spatially regulated expression, together with that of the related Scute (Sc) protein, helps define the pattern of Drosophila melanogaster sensory organs. We have examined the transcriptional control of the ac gene and shown, using in vivo assays, that several E-boxes, putative interacting sites for bHLH proteins, present in the ac promoter are most important for ac regulation. They most likely mediate ac self-stimulation and sc trans-activation. We also demonstrate that ac transcription is negatively regulated in vivo by the gene extramacrochaetae (emc) in a manner dependent on Ac and Sc products. emc encodes an HLH protein that lacks the basic region and presumably antagonizes Ac and Sc function by sequestering these proteins in complexes unable to interact with DNA. Our results strongly support the model of negative regulation of emc on ac and sc transcription through titration of their products. As currently thought, this seems accomplished by heterodimerization via the HLH domain, because an amino acid substitution in this region abolishes the emc antagonistic effect both in vitro and in vivo.

Amino Acid Sequence↗
PubMed1993

Molecular characterization of the lethal of scute genetic function.

The lethal of scute (l'sc) genetic function, which plays an essential role in the early development of the central nervous system of the Drosophila embryo, is localized within the achaete-scute complex (AS-C). Several lines of evidence have suggested that the AS-C T3 transcription unit corresponds to the l'sc function. We demonstrate that short fragments of DNA, containing the T3 transcribed region and a few kilobases of flanking sequences, rescue, albeit partially, the lethality and neural phenotype of l'sc deletions. Still, the complex wild-type pattern of expression of T3 is not reproduced by the transduced genes. This depends on cis-control elements scattered within the entire AS-C DNA and intermingled with regulatory elements specific for other AS-C transcription units. These elements are necessary for the initial activation of T3 in the neuroectoderm, probably mediated by axis-patterning genes. The presence of a cluster of E-boxes, upstream of the T3 transcribed region, suggests another level of control of T3 expression by basic-helix-loop-helix proteins, among them its own gene product.

Amino Acid Sequence↗
PubMed1992

Dtrk, a Drosophila gene related to the trk family of neurotrophin receptors, encodes a novel class of neural cell adhesion molecule.

We report the identification and molecular characterization of Dtrk, a Drosophila gene encoding a receptor tyrosine kinase highly related to the trk family of mammalian neurotrophin receptors. The product of the Dtrk gene, gp160Dtrk, is dynamically expressed during Drosophila embryogenesis in several areas of the developing nervous system, including neurons and fasciculating axons. gp160Dtrk has structural homology with neural cell adhesion molecules of the immunoglobulin superfamily and promotes cell adhesion in a homophilic, Ca2+ independent manner. More importantly, this adhesion process specifically activates its tyrosine protein kinase activity. These findings suggest that gp160Dtrk represents a new class of neural cell adhesion molecules that may regulate neuronal recognition and axonal guidance during the development of the Drosophila nervous system.

Amino Acid Sequence↗
PubMed1992

The extramacrochaetae gene provides information for sensory organ patterning.

The Drosophila adult epidermis displays a stereotyped pattern of bristles and other types of sensory organs (SOs). Its generation requires the proneural achaete (ac) and scute (sc) genes. In the imaginal wing disc, the anlage for most of the thoracic and wing epidermis, their products accumulate in groups of cells, the proneural clusters, whose distribution prefigures the adult pattern of SOs. These proteins then induce the emergence of SO mother cells (SMCs). Here, we show that the extramacrochaetae (emc) gene, an antagonist of the proneural function, is another agent that contributes to SO positioning. In the wing disc, emc is expressed in a complex and evolving pattern. SMCs appear not only within proneural clusters but also within minima of emc expression. When one of these spatial restrictions is eliminated, by ubiquitously expressing ac-sc, SMCs still emerge within minima of emc. When in addition, the other spatial restriction is reduced by decreasing emc expression, many ectopic SMCs emerge in a relatively even spaced and less constant pattern. Thus, the heterogeneous distribution of the emc product is one of the elements that define the positions where SMCs arise. emc probably refines SMC (and SO) positioning by reducing both the size of proneural clusters and the number of cells within clusters that can become SMCs.

Animals↗
PubMed1992

Patterning of the Drosophila nervous system: the achaete-scute gene complex.

The genes of the achaete-scute complex (AS-C) confer on cells the ability to become neural precursors. Their expression is restricted to groups of cells, the proneural clusters, which occupy specific positions within the embryo neural anlagen and the larva imaginal discs. Neuroblasts or sensory organ mother cells are born within these clusters. Thus, the patterns of expression of the AS-C genes help to define the topology of the nervous system.

Animals↗
PubMed1991

Cross-regulatory interactions between the proneural achaete and scute genes of Drosophila.

The achaete (ac) and scute (sc) genes of Drosophila allow cells to become sensory organ mother cells. Although ac and sc have similar patterns of expression, deletion of either gene removes specific subsets of sensory organs. This specificity was shown to reside in the peculiar regulation of ac and sc expression. These genes are first activated in complementary spatial domains in response to different cis-regulatory sequences. Each gene product then stimulates expression of the other gene, thus generating similar patterns of expression. Therefore, removal of one gene leads to the absence of both proneural gene products and sensory organs in the sites specified by its cis-regulatory sequences.

Animals↗
PubMed1991

Proneural clusters of achaete-scute expression and the generation of sensory organs in the Drosophila imaginal wing disc.

The proneural genes achaete (ac) and scute (sc) confer to Drosophila epidermal cells the ability to become sensory mother cells (SMCs). In imaginal discs, ac-sc are expressed in groups of cells, the proneural clusters, which are thought to delimit the areas where SMCs arise. We have visualized with the resolution of single cells the initial stages of sensory organ development by following the evolving pattern of proneural clusters and the emergence of SMCs. At reproducible positions within clusters, a small number of cells accumulate increased amounts of ac-sc protein. Subsequently, one of these cells, the SMC, accumulates the highest amount. Later, at least some SMCs become surrounded by cells with reduced ac-sc expression, a phenomenon probably related to lateral inhibition. Genetic mosaic analyses of cells with different doses of ac-sc genes, the sc expression in sc mutants, and the above findings show that the levels of ac-sc products are most important for SMC singling-out and SMC state maintenance. These products do not intervene in the differentiation of SMC descendants. The extramacrochaetae gene, an antagonist of proneural genes, negatively regulates sc expression, probably by interfering with activators of this gene.

Animals↗
PubMed1990

The Drosophila extramacrochaetae locus, an antagonist of proneural genes that, like these genes, encodes a helix-loop-helix protein.

The Drosophila extramacrochaetae (emc) locus participates in sensory organ patterning by antagonizing, in a mechanistically unknown way, the neurogenic activity of the achaete-scute complex (AS-C). Our cloning of emc DNA and molecular mapping of emc mutations have identified a transcription unit as the most likely candidate for the emc function. It encodes a protein that has a dimerizing helix-loop-helix (HLH) motif but lacks a basic region presumably important for DNA binding. AS-C and other proneural proteins have both domains. We propose that the emc product antagonizes neurogenesis by sequestering proneural proteins in complexes inefficient for DNA interaction. These and other findings suggest the existence of a network of synergistic and antagonistic interactions, mediated by HLH proteins, that participates in the establishment of the neural fate.

Amino Acid Sequence↗
PubMed1990

Competence to develop sensory organs is temporally and spatially regulated in Drosophila epidermal primordia.

The Drosophila adult cuticle displays a stereotyped pattern of sensory organs (SOs). Its deployment requires the expression of the achaete (ac) and scute (sc) genes. Their products confer to cells of epidermal primordia (imaginal discs and histoblasts) the ability to become SO precursors (SOPs). In imaginal discs, ac and sc expression is spatially restricted to cell clusters within which one or a few cells become SOP(s). With the help of ubiquitous sc expression provided at different developmental times by a heat shock-sc (HSSC) chimeric gene, we have analyzed the response of epidermal primordia to the proneural action of the sc product, and have tested whether the patterned distribution of ac/sc products is necessary to position SOs correctly within the epidermis. Each primordium responds to HSSC expression by developing SOs only during a characteristic developmental period. In the absence of the endogenous ac and sc genes, most SOs induced by HSSC are of the correct type and are located in wild type positions. These results indicate that the capacity of primordia to respond to sc is temporally and spatially regulated, that specification of the type of SO does not depend on ac/sc, and that SO positioning utilizes topological information independent of the spatially restricted distribution of ac/sc products.

Abdomen↗
PubMed1989

Molecular analysis of the asense gene, a member of the achaete-scute complex of Drosophila melanogaster, and its novel role in optic lobe development.

The achaete-scute complex (AS-C) comprises five genetic regions: achaete, scute (sc) alpha, lethal of sc, sc beta and sc gamma. Each region promotes the determination and positional specification of different, but partially overlapping, subsets of neural elements of Drosophila. In this work, we report a molecular characterization of the sc gamma region. It comprises 22 kb of DNA and contains two transcription units, only one of which, named asense (ase), seems involved in neurogenesis. ase encodes a protein that shares with other three AS-C proteins a domain containing a helix--loop--helix motif characteristic of a group of DNA-binding proteins. In the embryo, ase is expressed in neural precursor cells, a pattern consistent with the known requirement of sc gamma for the development of the larval nervous system. In late third-instar larvae, the gene is expressed in developing structures of the central nervous system (CNS), namely the anlagen of the optic lobes and in many cells, including neuroblasts, of the central brain and ventral ganglia. Its removal leads to anatomical defects in the adult optic lobes. This is the first demonstration of a role for the AS-C in the development of the adult CNS.

Amino Acid Sequence↗
PubMed1989

Search for Drosophila genes encoding a conserved domain present in the achaete-scute complex and myc proteins.

Several genes of the achaete-scute complex (AS-C) of Drosophila melanogaster encode a 60 amino acids long conserved domain which shares a significant homology with a region of the vertebrate myc proteins. Based on these results, the existence of a family of Drosophila genes that would share both this conserved domain and the neurogenic function of the AS-C has been postulated. To test this proposal, we have searched a D. melanogaster genomic library with a probe that encodes the conserved domain. Only under very low stringency hybridization conditions, clones not belonging to the AS-C cross-hybridized with the probe. Those that gave the strongest signals were characterized. Sequencing of the cross-hybridizing regions showed that they had no significant homology with the conserved domain, the sequence similarity extending at the most for 37 nucleotides. Although our results do not conclusively disprove the existence of a family of AS-C-like genes, they indicate that the conservation of the domain would be lower than that found for shared motifs in other families of Drosophila developmental genes.

Amino Acid Sequence↗
PubMed1989

Expression of achaete and scute genes in Drosophila imaginal discs and their function in sensory organ development.

Several kinds of sensory organs (SOs) appear in stereotyped positions on the adult Drosophila cuticle. The generation of these SOs requires the activity of the achaete (ac) and scute (sc) genes. To investigate whether ac and sc also provide spatial information for the positioning of SOs, we have analyzed the patterns of expression of these genes in the wing imaginal disc around the time that SO precursors are being specified. We find that expression coincides with and is restricted to areas of the disc where these precursors are known to be located. In the loss-of-function sc mutant, sc RNA is depleted in a single area located in the region where the precursor for the suppressed macrochaeta should be found. Moreover, some, and probably all, SOs require expression of these genes to reach the earliest detectable differentiated state. These and other results presented here, together with the finding that expansion of the areas of ac and/or sc expression causes the development of ectopic SOs, indicate that ac and sc promote the determination of SO precursors and delimit the regions of the imaginal discs where they can develop.

Animals↗
PubMed1988

A unitary basis for different Hairy-wing mutations of Drosophila melanogaster.

Hairy-wing (Hw) mutations are caused by modifications of the achaete-scute complex (AS-C) which promote development of extra sensory organs on the cuticle of Drosophila melanogaster. We show that the extreme Hw49c allele contains an inversion with a breakpoint within the AS-C, while the weak Hw685 allele is associated with a terminal deletion of the X chromosome which removes the achaete region of the AS-C. In both cases, foreign DNA in contact with the breakpoints presumably enhances expression of AS-C genes. Overexpression of achaete (T5) or scute alpha (T4) genes was previously found in Hw mutants associated with insertions of transposable elements (Hw1, HwBS and HwUa, Campuzano et al., 1986). In situ hybridizations to Hw49c and Hw1 larval sections show that the overexpression causes an abnormally generalized distribution of T4 and/or T5 transcripts in imaginal discs. Such distribution correlates with development of extra sensory organs in ectopic positions. We also show that in Hw685 a moderate overexpression of the T4 gene largely replaces the absence of the T5 gene in the development of the notum chaetae pattern. We propose that overexpression of T4/T5 genes in normal or ectopic positions is at the basis of the Hw effect.

Animals↗
PubMed1987

The achaete-scute complex is expressed in neurogenic regions of Drosophila embryos.

The achaete-scute gene complex (AS-C) of Drosophila melanogaster is involved in the development of the embryonic central nervous system and the cuticular sensory organs of both larva and adult. We have determined the embryonic spatial distributions of three transcripts encoded in the achaete, scute alpha and lethal of scute regions of the complex. The RNAs are present mainly between the blastoderm/early gastrula and the stage of germ band shortening. The patterns of expression are complex and evolve rapidly, affecting most or all of the known neurogenic regions. Gene expression precedes and is concomitant with the histological appearance of precursors of neural cells. These results support a role for the AS-C in determination and early differentiation of embryonic neural cells.

Journal Article↗